Electrical impedance myography as a biomarker of myostatin inhibition with ActRIIB-mFc: a study in wild-type mice

Abstract

Aim:

We sought to determine the sensitivity of electrical impedance myography (EIM) to myofiber hypertrophy induced by treatment with various doses of ActRIIB-mFc, an inhibitor of myostatin signaling.

Methods:

Wild-type C57BL/6 J mice (n = 40, male) were treated with three different doses of ActRIIB-mFc (i.e., RAP-031) or vehicle twice weekly for 5 weeks. End point assessments included gastrocnemius EIM, force measurements, muscle mass and myofiber size quantification.

Results:

ActRIIB-mFc increased body mass, muscle mass and myofiber size across all doses. Alterations in EIM 50 kHz phase and center frequency ( fc) were also present, with trends in a dose-dependent fashion. Significant correlations between EIM parameters and myofiber/functional data were identified.

Conclusion:

EIM outcomes can serve as effective biomarkers of myostatin signaling inhibition, demonstrating a dose sensitivity and correlation to standard assessments.

Lay abstract

We were interested in studying the sensitivity of a technique, called electrical impedance myography (EIM), to noninvasively assess the size of muscle fibers. In this technique a minute electrical current is used to probe the tissue. To do so, we gave a drug (ActRIIB-mFc) to mice that enlarges muscle fibers at three different doses. We were able to show that the EIM technique was able to detect this differential effect and functional changes induced by the drug correlated to the EIM data. This work suggests that EIM will be useful as a noninvasive marker muscle health.